The present invention is generally in the area of methods and devices to obtain vascular tissue grafts and more specifically in the area of methods and devices to obtain grafts, preferably autologous grafts, prepared from living vascular tissue.
Vascular grafts are commonly used by surgeons to bypass obstructions to blood flow caused by the presence of atherosclerotic plaques. Vascular grafts also are used in other applications such as providing arterial-venous shunts in dialysis patients, vascular repair or replacement and treating aneurysms. Grafts for bypass are often, but not exclusively, used in the coronary arteries, the arteries that supply blood to the heart. The materials used to construct a vascular graft usually are either synthetic or of biological origin, but combinations of synthetic and biological materials are under development. The most widely used biological vascular grafts are autologous saphenous vein or mammary artery. Some common synthetic grafts are made of polytetrafluoroethylene (PTFE) (e.g., GORTEX(trademark)) or polyester (e.g., DACRON(trademark)). Autologous grafts have generally been used more successfully than synthetic grafts. Autologous grafts remain patent (functional) much longer than synthetic grafts, and saphenous veins often fail in less than five years. The short lifetime of synthetic grafts is especially evident with small diameter (less than 7 mm diameter) grafts, as most small diameter synthetic grafts occlude within one to two years or less.
Small diameter vascular grafts are particularly used in coronary artery bypass surgery. Internal mammary artery (IMA) is the autologous graft of choice, because it typically has a longer life than venous grafts (95% patent at 5 years versus 85% patent at 2 years). Mammary arterial tissue, however, is difficult to harvest, typically is not available in lengths sufficient for multiple bypasses, and its removal can result in problems such as problematic wound healing. Moreover, obtaining sufficient venous tissue for repairing an occluded artery can be problematic in patients with venous conditions such as varicose veins and especially in second or third surgeries in the same patient. Recent literature also suggests that IMA used in bypass procedures either fails soon after transplantation or remains patent indefinitely. See, e.g., Bergsma, et al., Circulation 97(24):2402-05 (1998); Cooley, Circulation 97(24):2384-85 (1998). Other arteries such as the gastroepipolic, gastric, radial, and splenic also are used in coronary bypass procedures. Moreover, the recent American Heart Association/American College of Cardiology consensus document (Eagle, K. A., et al. xe2x80x9cACC/AHA Guidelines for coronary artery bypass graft surgery: A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelinesxe2x80x9d, Committee to Revise the 1991 Guidelines for Coronary Artery Bypass Graft Surgery, American College of Cardiology/American Heart Association, J. Am. Coll. Cardiol., 34(4):1262-347 (1999)) strongly recommends a move to total arterial revascularization.
In some cases, autologous or homologous saphenous vein preserved by freezing or other processes is used.
With people living longer, multiple surgeries are more common. At the same time, open-heart surgery is becoming routine, aided by the development of new, minimally invasive and xe2x80x9coff-pumpxe2x80x9d procedures that have dramatically simplified the surgery and reduced the recovery time.
Development of a longer lasting small-diameter vascular graft is the subject of much academic and industrial research. One current approach is to combine cell culture and biomaterials technologies to make a living, xe2x80x9ctissue engineeredxe2x80x9d graft. This effort, however, is hindered by the requirements of a successful graft: It should be self-repairing, non-immunogenic, non-toxic, and non-thrombogenic. The graft also should have a compliance comparable to the artery being repaired, be easily sutured by a surgeon, and not require any special techniques or handling procedures. Grafts having these characteristics are difficult to achieve. Despite the substantial effort to date and the potential for significant financial reward, academic and industrial investigators have failed to produce graft materials that have demonstrated efficacy in human testing.
Efforts to avoid or minimize the need for vascular grafts for repair of otherwise healthy vascular tissue have been described. For example, Ruiz-Razura et al., J. Reconstructive Microsurgery, 10(6):367-373 (1994) and Stark et al., Plastic and Reconstructive Surgery, 80(4):570-578 (1987) disclose the use of a round microvascular tissue expander for acute arterial elongation to examine the effects on the tissue of such acute hyperextension. The expander is a silicone balloon that is placed under the vessel to be elongated. The balloon is filled with saline over a very short period, causing acute stretching and elongation of the vessel. The method is purported to be effective for closure of arterial defects up to 30 mm without the need for a vein graft. These techniques are appropriate for trauma, but are not used for restoring blood flow in vessels that are occluded, for example by disease, which are treated by surgically bypassing the obstruction with a graft. The disclosed methods and devices fail to provide an autologous graft or versatile substitute. Moreover, the acute stretching may damage the vessel.
It is therefore an object of the present invention to provide devices and methods for creating natural blood vessel suitable for grafting.
It is another object of the present invention to provide devices and methods for making an autologous blood vessel graft.
It is further object of the present invention to provide devices and methods for creating blood vessel grafts in vivo or in vitro.
These and other objects, features, and advantages of the present invention will become apparent upon review of the following detailed description of the invention taken in conjunction with the drawings and the appended claims.
Devices and methods are provided for forming a vascular graft by axially distending a blood vessel to stimulate vessel growth. Preferably, the device is implanted, for example using endoscopic techniques, for use in vivo. A portion of a blood vessel (i.e. the donor vessel) then is distended using the device. Preferred donor vessels include the gastroepipolic artery, as well as the internal mammary, femoral, gastric, splenic, and radial arteries. Then, the in vivo distended portion of the donor vessel is excised, for example, at the time of bypass surgery. In an alternative embodiment, a section of donor vessel is surgically excised from the bypass surgery patient, preferably at the time of by-pass surgery, and then distended in vitro in a medium for cell growth, e.g., in an organ culture system or bioreactor. Where the donor is the recipient of the graft, the result using either approach advantageously is a totally autologous, living vascular graft.
In a preferred embodiment, the device comprises a stretching mechanism which includes (i) a stabilization rod, (ii) a pair of rotatable elements, wherein each rotatable element is rotatably attached to the elongated body and has a channel substantially perpendicular to the axis of rotation, and (iii) a means for rotating each rotatable element to axially distend a blood vessel positioned in the channels of the rotatable elements. The elements can be rotated intermittently, cyclically, or continuously, over a period to distend or elongate the donor vessel.
The rotatable elements can, in one embodiment, comprise a pair of arms extending from a central base, the arms being capable of bending or flexing between a straight configuration and a curved configuration. The straight configuration preferably is used to give the device a narrow profile suitable for endoscopic insertion into a donor patient. The arms can have an inherent spring action, such that the relaxed state of the arms is a curved configuration and wherein the arms will transform from the straight configuration into a curved configuration upon release of one or more releasable fasteners.
In another variation, the rotatable elements each comprise a pair of rounded lobes extending from a central base, the channel extending between each pair of lobes. The lobes can comprise a disk-shaped portion having an outer edge surface distal the axis of rotation of the rotatable element and a substantially flat upper surface distal the stabilization rod. The outer edge surface can include one or more grooves in which a blood vessel or portion thereof can be positioned, supported and guided during the stretching process.
The means for rotating can comprise a torsion spring and a cam mechanism for controlling the rotation position, and/or a prime mover that is mechanically, electromechanically, or hydraulically driven.
The device optionally can include a growth factor or other growth stimulating agent for release in an effective amount to enhance growth of the blood vessel. Such agents may be impregnated into the materials of construction forming the device or can be in the form of a coating or a reservoir device attached to the stretching device.
Also provided is an apparatus for extending a donor blood vessel of a human or animal in vitro. The apparatus includes a chamber containing a quantity of tissue culture growth medium; an inlet cannula extending through a first orifice in the chamber, the inlet cannula having a first end outside of the chamber and a second end positioned inside the chamber; an outlet cannula extending through a second orifice in the chamber, the outlet cannula having a first end outside of the chamber and a second end positioned inside the chamber; and a means, such as a linear motor, for moving the inlet cannula, the outlet cannula, or both, to axially stretch a donor blood vessel secured between the inlet cannula and the outlet cannula in a submerged position in the tissue culture growth medium. In operation, a donor blood vessel is secured by having a first end of the vessel secured to the second end of the inlet cannula and a second end of the vessel secured to the second end of the outlet cannula, thereby forming a conduit through the blood vessel and between the first end of the inlet cannula and the first end of the outlet cannula. Preferably, tissue culture growth medium flows through this conduit.